1. Field of the Invention
This invention relates to a process for preparing L-p-boronophenylalanine and an intermediate for preparing the same.
2. Prior Art
As a cancer treating method, a so-called neutron capturing method has been clinically employed only in Japan, but in recent years, it is now clinically applying also in the United States, Europe and Australia. Medicines which are now clinically applied are only BSH and L-p-boronophenylalanine. It is the sole medicine for treatment used not only for a skin cancer but also a cerebral tumor well taken therein, and has now been supplied from BBI Co. of U.S.A. It has now been synthesized by the method as shown below. ##STR2##
In this synthetic method, DL-isomers (racemic isomers) of p-boronophenylalanine are obtained (see H. R. Synder, A. J. Reedy and W. M. J. Lennarz, "J. Am. Chem. Soc." (1958), vol. 80, p.835) so that it is necessary to finally separate and purify the L-isomer by an optical resolution. Thus, the method is high in cost and a patient must pay the expenses for one treatment with several ten thousand dollars.
To solve the above problems, the following selective synthetic method of an optically active L-p-boronophenyl-alanine has been developed in recent years. ##STR3##
In the above-mentioned asymmetrically reducing method using a rhodium catalyst, an asymmetric yield is atmost 88% and requires to finally separate and purify the L-isomer (see E. G. Samsel, U.S. Pat. No. 5,157,149, 1992). Also, in the above method deriving from L-serine, there involves the problem that an yield of the coupling reaction with aryl iodide is low as 50 to 55% (see C. Malan and C. Morin, "SYNLETT", 1996, p.167).